PMID- 16012712
OWN - NLM
STAT- MEDLINE
DCOM- 20050919
LR  - 20181201
IS  - 1021-335X (Print)
IS  - 1021-335X (Linking)
VI  - 14
IP  - 2
DP  - 2005 Aug
TI  - Estrogen receptor-negative and human epidermal growth factor receptor 2-negative 
      breast cancer tissue have the highest Ki-67 labeling index and EGFR expression: 
      gene amplification does not contribute to EGFR expression.
PG  - 337-43
AB  - Estrogen receptor (ER) and human epidermal growth factor 2 (HER2) are 
      well-investigated molecules and the focus of many breast cancer therapies. There 
      is a group of breast cancers lacking ER and HER2, but it is not fully understood. 
      Treatment for these patients is limited to cytotoxic chemotherapy. The purpose of 
      present study is to examine ER(-)/HER2(-) breast cancers, with a particular focus 
      on epidermal growth factor receptor (EGFR). EGFR is a target molecule for which 
      novel medicines have been recently developed for other organ cancers, however 
      biological significance in breast cancer is not yet well demonstrated. Breast 
      cancer specimens (n=58) were categorized into four groups: i) ER(+)/HER2(-) 
      (51.7%); ii) ER(+)/HER2(+) (8.6%); iii) ER(-)/HER2(+) (20.7%); and iv) 
      ER(-)/HER2(-) (19.0%). They were immunohistochemically (IHC) examined using 
      antibodies for EGFR, platelet derived growth factor receptor (PDGFR)alpha, 
      PDGFRbeta, parathyroid hormone (PTH) receptor, Ki-67, cyclinD1, p53, and 
      vimentin. The Ki-67 labeling index (LI) was highest in ER(-)/HER2(-) (36.5%), and 
      decreased in order from ER(-)/HER2(+) (31.4%), ER(+)/HER2(+) (17.7%), to 
      (ER(+)/HER2(-) (15.9%) (p=0.001). EGFR, p53 and vimentin were highly expressed in 
      ER(-)/HER2(-) breast cancer cells (p<0.01). CyclinD1 was inversely expressed to 
      Ki-67 LI (p<0.001). Gene amplification of EGFR was examined by two in situ 
      hybridization techniques, fluorescence in situ hybridization (FISH) and 
      chromogenic in situ hybridization (CISH) in serial sections to IHC. Only 1 of 14 
      EGFR-positive breast cancers showed gene amplification at low levels by CISH. 
      Overall, the ER(-)/HER2(-) breast cancer showed the highest Ki-67 LI, the most 
      frequent expression of EGFR, p53 and vimentin, as well as the lowest expression 
      of cyclinD1. It is unlikely that gene amplification contributes to EGFR 
      expression. ER(-)/HER2(-) breast cancers have potential in the development of 
      novel therapeutics, including targeted medicines.
FAU - Umemura, Shinobu
AU  - Umemura S
AD  - Department of Pathology, Tokai University School of Medicine, Bohseidai, Isehara, 
      Kanagawa 259-1193, Japan. umemura@is.icc.u-tokai.ac.jp
FAU - Takekoshi, Susumu
AU  - Takekoshi S
FAU - Suzuki, Yasuhiro
AU  - Suzuki Y
FAU - Saitoh, Yuki
AU  - Saitoh Y
FAU - Tokuda, Yutaka
AU  - Tokuda Y
FAU - Osamura, R Yoshiyuki
AU  - Osamura RY
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Oncol Rep
JT  - Oncology reports
JID - 9422756
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (Receptors, Estrogen)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Biomarkers, Tumor/*analysis/genetics
MH  - Breast Neoplasms/genetics/metabolism/*pathology
MH  - ErbB Receptors/analysis/genetics
MH  - Female
MH  - Gene Amplification
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Ki-67 Antigen/analysis
MH  - Middle Aged
MH  - Receptor, ErbB-2/analysis
MH  - Receptors, Estrogen/analysis
EDAT- 2005/07/14 09:00
MHDA- 2005/09/20 09:00
CRDT- 2005/07/14 09:00
PHST- 2005/07/14 09:00 [pubmed]
PHST- 2005/09/20 09:00 [medline]
PHST- 2005/07/14 09:00 [entrez]
PST - ppublish
SO  - Oncol Rep. 2005 Aug;14(2):337-43.